Clinical Trials Register

Summary
EudraCT Number:	2015-005045-31
Sponsor's Protocol Code Number:	55668
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-02-25
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2015-005045-31

A.3

Full title of the trial

Switching to Tenofovir Alafenamide Fumarate or ABACavir in patients with Tenofovir Disoproxil Fumarate associated eGFR decline. A randomized clinical trial.

Switchen naar tenofovir alafenamide fumaraat of abacavir bij patienten met tenofovir disoproxil fumaraat geassocieerde eGFR-daling. Een gerandomiseerde klinische studie.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Switching to tenofovir alafenamide fumarate or abacavir in patients with renal impairment due to tenofovir disoproxil fumarate.

Overgaan naar tenofovir alafenamide fumaraat of abacavir bij patienten met een nierfunctieverslechtering door tenofovir disoproxil fumaraat.

A.3.2

Name or abbreviated title of the trial where available

BACTAF

A.4.1

Sponsor's protocol code number

55668

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Erasmus MC
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Gilead Sciences Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Erasmus MC
B.5.2	Functional name of contact point	Coordinerend onderzoeker
B.5.3	Address:
B.5.3.1	Street Address	's Gravendijkwal 230
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3015 CE
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31631090143
B.5.6	E-mail	i.wijting@erasmusmc.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Descovy
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	FTC/TAF 200mg/10mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EMTRICITABINE
D.3.9.1	CAS number	143491-57-0
D.3.9.2	Current sponsor code	FTC
D.3.9.4	EV Substance Code	SUB01882MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.1	CAS number	379270-37-8
D.3.9.2	Current sponsor code	GS-7340
D.3.9.3	Other descriptive name	TENOFOVIR ALAFENAMIDE
D.3.9.4	EV Substance Code	SUB121761
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Descovy
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	FTC/TAF 200mg/25mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EMTRICITABINE
D.3.9.1	CAS number	143491-57-0
D.3.9.2	Current sponsor code	FTC
D.3.9.4	EV Substance Code	SUB01882MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.1	CAS number	379270-37-8
D.3.9.2	Current sponsor code	GS-7340
D.3.9.3	Other descriptive name	TENOFOVIR ALAFENAMIDE
D.3.9.4	EV Substance Code	SUB121761
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Kivexa
D.2.1.1.2	Name of the Marketing Authorisation holder	Viiv Healthcare
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Renal safety of switching from TDF to TAF or ABC in patients with TDF-associated eGFR-decline.

renale veiligheid van switchen van TDF naar TAF of ABC bij patienten met een TDF-geassocieerde eGFR-daling.

E.1.1.1

Medical condition in easily understood language

Therapy of HIV

Behandeling van HIV

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To study the renal safety when HIV patients with TDF related renal toxicity switch to TAF compared to the current practice of switching to ABC.

Bestuderen van renale veiligheid wanneer HIV-patienten met TDF-gerelateerde nefrotoxiciteit switchen naar TAF in vergelijking met switchen naar ABC volgens huidige richtlijn.

E.2.2

Secondary objectives of the trial

To evaluate effect and safety of a switch from TDF to TAF or ABC on viral suppression, markers of proximal tubular dysfunction, other biochemical markers (liver, lipids, inflammation), bone mineral density, Framingham risk score.

Bestuderen van effect en veiligheid van switch van TDF naar TAF of ABC op virale suprressie, markers van proximale tubulaire dysfunctie, andere biochemische markers (lever, lipiden, inflammatie), botdichtheid en Framingham risk score.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

18 years or older
HIV-positive with HIV-RNA <50 c/ml for at least 6 months
Stable on TDF/FTC or TDF/3TC for at least 12 months, in combination with a 3rd antiretroviral agent
Confirmed/probable TDF-related eGFR-decline with absence of other causes of eGFR-decline.
HLA-B5701 allele negative
General medication and condition does not interfere with trial procedure.

18 jaar of ouder
HIV-positief met HIV-RNA < 50 c/ml voor minimal 6 maanden
Stabiel op TDF/FTC of TDF/3TC voor minimal 12 maanden, in combinatie met een 3e antiretrovirale middle
Bevestigde of waarschijnlijke TDF-gerelateerde eGFR-daling met afwezigheid van andere redenen voor eGFR-daling
HLA-B5701 negatief
Medische conditie en medicatie interfereert niet met studie procedure

E.4

Principal exclusion criteria

Chronic hepatitis B or C
Symptomatic arterial disease e.g. a history of coronary artery disease, ischemic cerebrovascular accident or claudication intermittens in medical history
Not meeting all inclusion-criteria as mentioned above

Chronische hepatitis B of C
Symptomatisch arterieel lijden, zoals een voorgeschiedenis van coronairlijden, ischemisch CVA of claudicatio intermittens in voorgeschiedenis
Niet voldoend aan alle inclusie-criteria zoals boven genoemd

E.5 End points

E.5.1

Primary end point(s)

To evaluate the extent of recovery of TDF-based eGFR decline in the TAF-arm versus the ABC-arm at week 48 after the switch from TDF. Recovery is defined as the time to the first eGFR during follow up to within 85% of the eGFR at TDF initiation

Tijd tot herstel van eGFR in TAF-arm versus in ABC-arm gedurende 48 weken na switch vanaf TDF. Herstel is gedefinieerd als tijd tot eerste eGFR binnen 85% van eGFR op moment van start TDF.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 48

na 48 weken

E.5.2

Secondary end point(s)

• The between group differences (TAF vs ABC) with respect to the time to recovery of renal dysfunction at week 96, with adjustment for potential important confounders.
• HIV-RNA suppression rate <50 ABC versus TAF at week 48 and 96.
• The mean eGFR at week 48 and 96 on ABC and TAF will be compared to week 0. The slopes of eGFR-decline between week 0 and week 48 or 96 between the different groups (ABC, TAF).
• Tolerability of TAF, defined in terms of compliance (%) and adverse events (%).
• The median (IQR) of uPCR, uACR, uAPR, uB2MG/CR within and between the ABC and TAF group and changes at week 48 or 96 compared to week 0.
• The proportion of patients with at least 2 markers of PTD (either one of the following: normoglycemic glycosuria, hypophosphatemia (PO4<0.8) with FEPO>10%, uPCR >15 with uAPR<0.4, non-anion gap metabolic acidosis) within and between groups.
• Framingham risk-score, inflammation parameters, blood pressure, pulse rate and lipids will be evaluated between groups and within groups at week 0, 48 and 96.
• Bone mineral density (BMD) of spine and hip will be compared in and between groups (ABC, TAF) at week 0, 48 and 96.

- verschillen tussen groepen (TAF vs ABC) met oog op tijd tot herstel van eGFR na 96 weken, correctie voor confounders.
- HIV-suppressie < 50 c/mL tussen groepen op W48 en W96
- gemiddelde eGFR op W48 en W96 in vergelijking met week 0. Hellingen van eGFR-daling tussen week 0 en week 48 of 96 tussen de groepen.
- Tolerabiliteit van TAF, gedefinieerd in compliantie en bijwerkingen
- gemiddelde van uPCR, uACR, uAPR, uB2MG/CR binnen en tussen groepen en veranderingen op W48 en W96 in vergelijking met W0.
- proportie patienten met minimal 2 markers voor proximale tubulaire dysfunctie (normoglycaemische glucosurie, hypofosfatemie met fractionele fosfaatexcretie >10%, uPCR>15 met uAPR<0.4, non-anion-gap metabole acidose) in en tussen groepen.
- Framingham risk-score, inflammatieparameters, bloeddruk, pols, lipiden binnen en tussen groepen op W0, W48 en W96.
- Botdichtheid van wervelkolom en heup binnen en tussen groepen op W0, W48 en W96.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 0, Week 48, Week 96

Week 0, week 48, week 96

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of trial is when the last person included completes his/her last visit at week 96.

Einde van de studie is wanneer de laatst geincludeerde persoon completeert zijn/haar laatste bezoek op week 96.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the trial, patients will be offered treatment according the current standard of care for HIV-1 infected patients or to continue TAF.

Na de studie zal patienten behandeling gegeven worden volgens de huidige standaard voor zorg voor HIV-1 geinfecteerde patienten, of ze zullen de TAF continueren.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-02-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-13

P. End of Trial
P.	End of Trial Status	Ongoing

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